The present invention relates to catalyst compounds and processes for carbon-carbon bond formation, and particularly for alkene or aromatic acylation, alkoxylation or alkylation reactions.
The most widespread of these reactions is the Friedel-Crafts reaction, the activating agents for which are relatively low cost and enable a wide variety of organic manufacturing processes. Other reactions include the Diels-Alder and Kondakov reactions.
These reactions however present the manufacturer with a number of challenges, including the handling of raw materials, the handling of solvents, process conditions and effluent control. For example, such reactions often require the use of acyl halides, Lewis acid activating agents (typically AlCl3, TiCl4, BF3) and halogenated solvents. The handling of these can present significant health, safety and environmental problems, especially for the batch processing typically used by smaller companies or for smaller quantity production.
Also because the activating agent is typically decomplexed from the product by the use of water, there is a considerable amount of aqueous effluent generated, which must be treated to be environmentally acceptable.
Furthermore, the activating agent, although sometimes called a catalyst, is not a true catalyst since it usually has to be present in more or less stoichiometric amounts, and the decomplexing hydration effectively renders the agent non-reusable.
There have been proposals for various catalysts and processes as substitutes, and although some of these have had limited success for specific starting materials or types of starting materials, there has been no proposal of which we are aware which would be generally applicable over a wide range of starting material, which would use truly catalytic materials and quantities and which would not pose other problems as severe as those encountered in the classical Friedel-Crafts situation.
Reviewing current industrial practice in more detail, typical raw material feedstocks are (1) substituted aromatics (alkylbenzenes, tetralins, naphthalenes, thiophenes, phenols), alkenes; (2)acylating agentsxe2x80x94acyl halides (acetyl chloride, benzoyl chloride), acyl anhydrides, epoxides (ethylene/propylene oxide) and fatty acids; (3) Lewis acidsxe2x80x94(AlCl3, TiCl4, BF3) and (4) solventsxe2x80x94such as dichloroethane/methane, chlorobenzene and nitro-solvents.
A generic example is as follows: 
Typically, alkenes or substituted aromatics are reacted in the presence of a Lewis acid activating agent with an acyl chloride or anhydride to give ketones, or with an epoxide to give an oxalkylated product. The Lewis acid is present in at least stoichiometric amounts and the reactions nearly always require a polar solvent.
Strictly speaking the Lewis acids (typically AlCl3, TiCl4) used are not true catalysts as they are used in stoichiometric amounts or more. This is because they form complexes with product compounds which are more strongly bonded than with the reagents and this requires a destructive method (aqueous hydrolysis) of retrieving the product, so the Lewis acids are non-recoverable.
AlCl3, TiCl4 and FeCl3 have the advantage of ready economic supply. Other more exotic and expensive Lewis acid catalysts are used in different parts of the chemical industry.
A Friedel-Crafts acylation reaction will end up with the product as a complex with the Lewis acid activating agent. These complexes are solids if isolated (which is unusual) but in practice the polar solvent typically employed keeps them in liquid phase and prevents potential abrasion of the reactor wall. The products are liberated by the addition of water which also reacts with the freed activating agent to generate a large volume of a non-recoverable effluent stream.
The acyl halides and Lewis acids are moisture-sensitive with the risk of liberation of hydrogen halides (usually as hydrogen chloride). Additionally, solid Lewis acids can present both dust and mechanical erosion problems. Reactions tend to be very fast and the time taken is directly related to heat removal from the plant. They are normally run in semi-batch mode to deal with their exothermicity, with efficient cooling or low boiling solvent reflux to take the required heat out of the system.
Reaction mixtures are usually quenched into water/ice to break the complex of catalyst and product. The resulting aqueous effluent has to be treated. Products are then recovered by solvent extraction, considerable washing (hence more effluent), solvent recovery and recrystallisation or distillation to purify the product, incurring relatively high energy costs.
Waste disposal for these reactions is expected to be subject to more stringent legislation, and to be a source of increasing cost. Waste disposal methods vary, but normally the major waste is precipitated metal hydroxide/salts, which goes to landfill unless an alternative use, e.g. as a flocculating agent, can be found.
Existing plant can be used for these reactions provided it is acid-resistant (especially to HCl). This generally rules out stainless steel and the ideal is glass-lined equipment.
The problems with these reactions are well known, and various solutions have been proposedxe2x80x94see for example Pearson and Buehler, xe2x80x9cFriedel-Crafts Acylations with Little or No Catalystxe2x80x9d, Synthesis, 1972, 533-542. Success has been limited, usually with a catalyst being found suitable only for one substrate/agent, or only in very specific conditions.
An ideal solution to the problems would include as many as possible of the following criteria:
1) the reaction should be truly catalytic, preferably giving desired selectivity
2) the catalyst should (a) not form a strong complex with the product (b) be recyclable (c) have no deleterious effect on the end product (d) not be limited by mass transfer problems
3) non-halogenated reagents could be used e.g. acids, esters or anhydrides
4) no solvents or only non-halogenated (preferably hydrocarbon) catalyst solvents would be preferable, though a fluorinated solvent would be acceptable if not soluble or can be rendered insoluble in or immiscible with the organic reaction phase.
Where there is no carboxy group in the product, as in alkylation, complexation will frequently not be a problem; but most of the other criteria apply.
The present invention is concerned with fluorinated sulfonyl compounds and their use in catalysis.
Nishikido et al, Synlett, 1998, 1347 have disclosed a lanthanide compoundxe2x80x94ytterbium triflamide, Yb[N(SO2C4F9)2]3xe2x80x94as a catalyst, which may be used in catalysis of Friedel-Crafts and Diels-Alder reactions. See also Zhu, Synthesis, 1993, 953.
WO-A-97/11930 shows Bismuth triflate, Bi(OSO2CF3)3, as a catalyst. Kobayashi et al, Synlett 1994, 545 have demonstrated that lanthanum and hafnium triflates are catalysts for Friedel-Crafts acylation reactions.
Turowsky and Seppelt, Inorg. Chem., 1988, 27, p2135, have disclosed the preparation of HC(SO2CF3)3.
In the Journal of Organic Chemistry 1999, 64, p2910, Waller et al disclose the compounds Yb and Sc [C(SO2CF3)3]3, as aromatic nitration catalysts. They name the compounds xe2x80x9ctriflidesxe2x80x9d. They also disclose a method for their synthesis.
The present invention utilizes, to fulfil one or more of those desirable criteria listed above, the use of a fluorosulfonylmethide compound represented by the formula I:
M[C(SO2R1)3xe2x88x92(m+q)(SO2R2)m(SO2R3)q]x
where
M is H, Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Zr, Hf, Th, Nb, Ta, U, Bi, Al, Ga, In or Tl
x is the common oxidation state of a said metal M
R1, R2 and R3 are perfluorinated or polyfluorinated hydrocarbon, ether or amine moieties
and m+q=0, 1, 2 or 3 (m and q being zero or integers)
as catalyst in a Cxe2x80x94C bond formation reaction and in particular an acylation, alkylation or alkoxylation reaction.
The compound is used in catalytic quantities, for example 10 mol % or less based on the substrate of the reaction. Amounts of 5 mol % or less are effective, down to 1 mol % or below or even 0.1 mol % or below. Quantities below 0.001 mol % are unlikely to be practical.
The compound may be hydrated, and one or more of the said groups attached to a metal M i.e. within the square brackets of Formula 1, may be different from other(s) of those groups.
The common oxidation state (x) of Sc, Y, La, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Bi, Al, Ga, In and Tl is +3; the common oxidation state of Zr, Hf, Ce and Th is +4; the common oxidation state of Nb and Ta is +5; the common oxidation state of U is +6. The hydration number of the metal can be between 0 and 9 depending on the preparation and pre-treatment of the catalyst, but the preferred hydration number is 0. Suitable catalysts according to the process have R1, R2 and/or R3 groups which are perfluorinated or polyfluorinated alkyl (including cycloalkyl), ether or amine groupings where a carbon atom is bound directly to the sulfur. Preferred groups include CF3, C4F9, C6F13, C8F17, C2F4C4H9, C2F4OC4F9, C2F4N(C4F9)2.
Preferred R1, R2 and R3 groups are perfluorinated alkyl of C3 or greater of the formula CnF2n+1 where n is 2 or more, more preferably 6 or more, but preferably not more than 20. Especially effective are compounds where n=2,4, 6 or 8 and R1xe2x95x90R2 (alternatively stated, m and q are both 0). The alkyl groups may be linear, branched chain or cyclic or a combination thereof.
We also provide compounds per se of the formula I above (other than those where M=(H, Yb or Sc), and R1xe2x95x90R2xe2x95x90CF3) especially those compounds where in the group Cn F2n+1, n=2, 4, 6 or 8 and R1xe2x95x90R2. We find that these higher compounds, especially where nxe2x89xa74 are particularly applicable to catalysis of the formation of Cxe2x80x94C bonds on less reactive substrates such as toluene and xylene.
Furthermore we provide methods for the preparation of these compounds which differ from that proposed by Waller et al. We have found that if the scheme proposed by Waller et al is followed for other than CF3xe2x80x94containing compounds, the flate rather than the desired flide is obtained.
We therefore provide a method for the preparation of compounds of the formula I, other than these where R1xe2x95x90R2xe2x95x90R3xe2x95x90CF3 which includes the step of separating the desired flide as its alkali metal salt, usually its Lithium salt, from the analogue triflate salt by separation out of aqueous solution rather than by precipitation as in Waller et al.
We follow the nomenclature xe2x80x9c - - - flidexe2x80x9d for the compounds of the formula I given and defined above. For example, where n=1 they are xe2x80x9ctriflidesxe2x80x9d and where n=4, xe2x80x9cnonaflidesxe2x80x9d. We have found that these compounds, especially where n=4, 6 or 8, are more acidic and more generally applicable catalysts than triflates or triflamides. They have, moreover, the advantage that they are for the most part usable in a fluorous phase and in particular in a biphasic fluorous system (Horvath et al, Science 1994, 266, 72): this is believed to be due to the high fluorine content in these long-chain xe2x80x9cponytailsxe2x80x9d.
Biphasic operation allows for a particularly simple and efficient recycling of catalyst.
The Cxe2x80x94C bond formation process can be conducted at any combination of temperatures and pressures at which the process proceeds to form the desired product, e.g. an acyl arene. Reaction conditions suitable for practising the present invention will vary depending upon the arene, the acylating agent, the solvent and the catalyst according to the process. The rate of formation of the acyl arene will depend on the concentrations of arene, acylating agent, catalyst and the temperature.
Acylating agents to be used in the present process have the general structure RCOX where X is either Cl, OH or OCOR (i.e. acid anhydride) and R represents alkyl or aryl substituents. Preferred acylating agents according to the present process are acetic anhydride, acetic acid, benzoic anhydride, benzoic acid, isobutyric anhydride, isobutyric acid, pivalic anhydride, pivalic acid, propionic anhydride and propionic acid. Mixed anhydrides may be used. The acylation may also be of intramolecular nature and the preferred acylating agent is then a pendant carboxylic acid to form variously 5, 6 or 7 membered rings.
Alkoxylating agents include alkane epoxides.
Arenes capable of being treated according to the present process are those containing at least one aromatic ring; the word xe2x80x9caromaticxe2x80x9d refers to an unsaturated cyclic system well understood by those in the art. A representative summary of arenes capable of undergoing acylation is presented in Advanced Organic Chemistry, 4th Edition, Wiley-Interscience, 1992. Such arenes include benzene, substituted benzenes, fused aromatics where the arene is naphthalene, anthracene, phenanthrene and their derivatives, aromatic heterocycles such as furan, pyrrole, thiophene and their derivatives. Acylation of arenes more deactivated than monohaloarenes is currently not possible, where xe2x80x9cdeactivatedxe2x80x9d is a measure of reactivity well understood by those in the art Arenes which possess a single aromatic benzenoid ring are represented by Formula A. 
wherein R4 and R5 are independently selected from a hydrogen atom, a primary, secondary or tertiary alkyl having from 1 to 6 carbon atoms, a benzene ring or fused ring, which may be substituted, and a halide (i.e. fluoride, chloride, bromide or iodide) and u is zero or an integer which is 1 to 4 with the proviso that if R4 or any R5 is halide then other R5 or R4 cannot be halide, OCH3, OC2H5, OC3H7, OPh or NHCOCH3.
Preferred arenes according to Formula A include benzene, toluene, ethylbenzene, t-butylbenzene, chlorobenzene, anisole, acetanilide, biphenyl, m-xylene, p-xylene, cumene, bi and multicyclic and fused-ring aromatics such as naphthalenes and anthracenes.
Arenes to be treated according to the present process include heteroaromatics examples of which are furan, thiophene and pyrrole and substituted derivatives of these.
The arenes can be subjected to the present process to form the corresponding acyl or alkoxy arene in the appropriate position according to the theory of electrophilic substitution well understood by those in the art. Those of skill in the art can readily identify those arenes which are capable of being converted to valuable commercial products using the claimed process.
Acylated arenes of particular interest made by the claimed process are acetophenone, p-chloroacetophenone, p-methoxyacetophenone and 2-acetylthiophene and 4-isobutyroyltoluene.
The Cxe2x80x94C bond formation catalysed may be intramolecular, including cyclisation and hydroxyalkylation.
As has already been noted, a solvent may be used in the present process although the arene, other substrate and/or other reactive component may serve as the reaction medium. Preferred processes employ a solvent. Suitable solvents for practising the current process include any solvent or mixture of solvents wherein the solvent is inert with respect to the reactants under the particular process conditions. The term xe2x80x9cinertxe2x80x9d means that the solvent will not react with any other component of the reaction mixture: the arene, the acylating agent, the catalyst, the product and the side-product. Many solvents can be used including selected hydrocarbons, chlorinated hydrocarbons and other solvents. Examples are dichloromethane, 1,2-dichloroethane and benzotrifluoride. In the most preferred process, the solvent is fluorous and examples include perfluoromethyldecalin, perfluoroheptane, perfluoromethylcyclohexane and FC-88.
When no other material is added as solvent, the catalyst compound may subsequent to completion of the reaction be removed by preferential transfer into a solvent for that compound, e.g. a fluorous medium.